CLDN9

Summary

CLDN9 (claudin 9, HGNC:2051) is a protein-coding gene on chromosome 16p13.3, encoding Claudin-9 (O95484). Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.

This gene encodes a member of the claudin family. Claudins are integral membrane proteins and components of tight junction strands. Tight junction strands serve as a physical barrier to prevent solutes and water from passing freely through the paracellular space between epithelial or endothelial cell sheets, and also play critical roles in maintaining cell polarity and signal transductions. This protein is one of the entry cofactors for hepatitis C virus. Mouse studies revealed that this gene is required for the preservation of sensory cells in the hearing organ and the gene deficiency is associated with deafness.

Source: NCBI Gene 9080 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hearing loss, autosomal recessive 116 (Moderate, ClinGen)
• Clinical variants (ClinVar): 73 total — 1 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 5
• MANE Select transcript: NM_020982

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2051
Approved symbol	CLDN9
Name	claudin 9
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000213937
Ensembl biotype	protein_coding
OMIM	615799
Entrez	9080

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000445369

RefSeq mRNA: 1 — MANE Select: NM_020982 NM_020982

CCDS: CCDS10487

Canonical transcript exons

ENST00000445369 — 1 exons

Exon	Start	End
ENSE00001725039	3012923	3014505

Expression profiles

Bgee: expression breadth ubiquitous, 142 present calls, max score 86.29.

FANTOM5 (CAGE): breadth broad, TPM avg 3.0376 / max 97.6947, expressed in 214 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
152355	2.7149	201
152357	0.2137	99
152356	0.1090	76

Top tissues by expression

280 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	86.29	gold quality
cerebellar hemisphere	UBERON:0002245	86.04	gold quality
cerebellar cortex	UBERON:0002129	85.86	gold quality
pituitary gland	UBERON:0000007	85.40	gold quality
adenohypophysis	UBERON:0002196	84.59	gold quality
cerebellum	UBERON:0002037	83.33	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.21	gold quality
parotid gland	UBERON:0001831	75.60	gold quality
endometrium epithelium	UBERON:0004811	73.84	gold quality
blood	UBERON:0000178	73.04	gold quality
sperm	CL:0000019	73.02	gold quality
male germ cell	CL:0000015	72.43	gold quality
body of pancreas	UBERON:0001150	72.36	gold quality
right uterine tube	UBERON:0001302	72.02	gold quality
right lobe of liver	UBERON:0001114	71.59	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	71.20	gold quality
apex of heart	UBERON:0002098	69.70	gold quality
triceps brachii	UBERON:0001509	69.47	gold quality
spinal cord	UBERON:0002240	69.22	gold quality
pancreas	UBERON:0001264	69.01	gold quality
putamen	UBERON:0001874	68.47	gold quality
right frontal lobe	UBERON:0002810	67.95	gold quality
gluteal muscle	UBERON:0002000	67.71	gold quality
heart right ventricle	UBERON:0002080	66.84	gold quality
caudate nucleus	UBERON:0001873	66.75	gold quality
epithelium of bronchus	UBERON:0002031	66.54	silver quality
bronchus	UBERON:0002185	66.03	silver quality
mucosa of transverse colon	UBERON:0004991	65.80	gold quality
central nervous system	UBERON:0001017	65.66	gold quality
bronchial epithelial cell	CL:0002328	65.60	silver quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.36
E-MTAB-7303	no	358.91

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

36 targeting CLDN9, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-3147	99.52	66.34	388
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-6799-5P	99.14	65.72	2093
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-5197-3P	98.71	67.05	1905

Literature-anchored findings (GeneRIF, showing 13)

• CLDN9, clustered with CLDN6 at human chromosome 16p13.3, is a four-transmembrane protein with WWCC motif, defined by W-X(17-22)-W-X(2)-C-X(8-10)-C. (PMID:12736707)
• Residues N38 and V45 in the first extracellular loop (EL1) of CLDN9 are necessary for HCV entry. (PMID:17804490)
• claudin-6 and claudin-9 expressed in CD81+ cells also enable the entry of HCV pseudoparticles derived from six of the major genotypes. (PMID:18234789)
• Mouse studies suggest that claudin-9 deficiency may cause hearing loss not only in mice but also in humans. (PMID:19696885)
• Claudins 6, 7, and 9 expressions are closely related to gastric carcinogenesis. (PMID:19960275)
• Increased expression of claudin-6, claudin-7, or claudin-9 is sufficient to enhance tumorigenic properties of a gastric adenocarcinoma cell line. (PMID:20874001)
• Although claudin-6 and claudin-9 can serve as entry factors in cell lines, hepatitis C virus infection into human hepatocytes is not dependent on claudin-6 and claudin-9. (PMID:23864633)
• CLDN9 may be an important biomarker for invasive pituitary oncocytomas. (PMID:25281028)
• the expression of claudin-5 and claudin-9 was down-regulated while the expression of claudin-8 was up-regulated in cervical carcinoma tissues compared with adjacent non-neoplastic tissues. (PMID:26464708)
• these results suggest that Helicobacter pylori lipopolysaccharide induces TLR2 expression in the gastric adenocarcinoma cells, and that the longer the exposure to lipopolysaccharide, the greater the expression of TLR2 in the cell membrane; consequently the expression of claudin-4, -6, -7 and -9 also increases (PMID:29031421)
• We conclude that CLDN9 is essential for proper audition in humans and its disruption leads to SNHL in humans. (PMID:31175426)
• Claudin9 is a novel prognostic biomarker for endometrial cancer. (PMID:36129146)
• Pharmacological Activity of Matrine in Inhibiting Colon Cancer Cells VM Formation, Proliferation, and Invasion by Downregulating Claudin-9 Mediated EMT Process and MAPK Signaling Pathway. (PMID:37719361)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cldn9	ENSMUSG00000066720
rattus_norvegicus	Cldn9	ENSRNOG00000089717

Paralogs (22): CLDN11 (ENSG00000013297), CLDN18 (ENSG00000066405), CLDN15 (ENSG00000106404), CLDN16 (ENSG00000113946), CLDN10 (ENSG00000134873), CLDN17 (ENSG00000156282), CLDN8 (ENSG00000156284), CLDN14 (ENSG00000159261), CLDN1 (ENSG00000163347), CLDN19 (ENSG00000164007), CLDN3 (ENSG00000165215), CLDN2 (ENSG00000165376), CLDN20 (ENSG00000171217), CLDN22 (ENSG00000177300), CLDN7 (ENSG00000181885), CLDN5 (ENSG00000184113), CLDN6 (ENSG00000184697), CLDN24 (ENSG00000185758), CLDN4 (ENSG00000189143), CLDN25 (ENSG00000228607), CLDN34 (ENSG00000234469), CLDN23 (ENSG00000253958)

Protein

Protein identifiers

Claudin-9 — O95484 (reviewed: O95484)

All UniProt accessions (1): O95484

UniProt curated annotations — full annotation on UniProt →

Function. Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity. (Microbial infection) Acts as a receptor for hepatitis C virus (HCV) entry into hepatic cells.

Subunit / interactions. Interacts with CLDN1, CD81 and OCLN.

Subcellular location. Cell junction. Tight junction. Cell membrane.

Tissue specificity. Expressed in the liver, in peripheral blood mononuclear cells and hepatocarcinoma cell lines.

Disease relevance. Deafness, autosomal recessive, 116 (DFNB116) [MIM:619093] A form of non-syndromic deafness characterized by slowly progressive, moderate to profound sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the claudin family.

RefSeq proteins (1): NP_066192* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003553	Claudin9	Family
IPR004031	PMP22/EMP/MP20/Claudin	Family
IPR006187	Claudin	Family
IPR017974	Claudin_CS	Conserved_site

Pfam: PF00822

UniProt features (29 total): strand 9, topological domain 5, helix 5, mutagenesis site 4, transmembrane region 4, chain 1, region of interest 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6OV2	X-RAY DIFFRACTION	3.2
6OV3	X-RAY DIFFRACTION	3.25

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95484-F1	80.95	0.42

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (4):

Position	Phenotype
38	mildly decrease hcv infection susceptibility in cell culture.
43	no effect on hcv infection susceptibility in cell culture.
45	abolishes hcv infection susceptibility in cell culture.
53	no effect on hcv infection susceptibility in cell culture.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-420029	Tight junction interactions

MSigDB gene sets: 115 (showing top): MODULE_52, GCANCTGNY_MYOD_Q6, MODULE_45, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GOBP_APICAL_JUNCTION_ASSEMBLY, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, KEGG_TIGHT_JUNCTION, MODULE_16, GOBP_CELL_CELL_ADHESION, MODULE_118, GOBP_CELL_JUNCTION_ORGANIZATION, MYOD_01, MODULE_379, GOBP_BIOLOGICAL_PROCESS_INVOLVED_IN_INTERACTION_WITH_HOST

GO Biological Process (6): cell adhesion (GO:0007155), calcium-independent cell-cell adhesion (GO:0016338), bicellular tight junction assembly (GO:0070830), cell-cell junction organization (GO:0045216), symbiont entry into host cell (GO:0046718), tight junction organization (GO:0120193)

GO Molecular Function (4): virus receptor activity (GO:0001618), structural molecule activity (GO:0005198), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (5): plasma membrane (GO:0005886), bicellular tight junction (GO:0005923), cell junction (GO:0030054), membrane (GO:0016020), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Cell-cell junction organization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cellular process	1
cell-cell adhesion	1
apical junction assembly	1
tight junction assembly	1
cell junction organization	1
viral life cycle	1
symbiont entry into host	1
cell-cell junction organization	1
symbiont entry into host cell	1
exogenous protein binding	1
molecular_function	1
protein binding	1
binding	1
membrane	1
cell periphery	1
apical junction complex	1
tight junction	1
cell junction	1

Protein interactions and networks

STRING

812 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLDN9	TJP2	Q9UDY2	698
CLDN9	CLDN12	P56749	688
CLDN9	TJP1	Q07157	666
CLDN9	CLDN6	P56747	648
CLDN9	OCLN	Q16625	640
CLDN9	CD81	P18582	598
CLDN9	NPC1L1	Q9UHC9	511
CLDN9	ILDR1	Q86SU0	465
CLDN9	TJP3	O95049	455
CLDN9	CLDN14	O95500	452
CLDN9	MARVELD2	Q8N4S9	450
CLDN9	SCARB1	Q8WTV0	448
CLDN9	EPHA2	P29317	447
CLDN9	TFRC	P02786	416
CLDN9	PCDHB5	Q9Y5E4	406
CLDN9	ASGR2	P07307	406

IntAct

184 interactions, top by confidence:

A	B	Type	Score
CLDN9	PLPPR2	psi-mi:“MI:0915”(physical association)	0.560
CLDN9	AMIGO1	psi-mi:“MI:0915”(physical association)	0.560
LPAR3	CLDN9	psi-mi:“MI:0915”(physical association)	0.560
CYB561	CLDN9	psi-mi:“MI:0915”(physical association)	0.560
IGFBP5	CLDN9	psi-mi:“MI:0915”(physical association)	0.560
VSTM1	CLDN9	psi-mi:“MI:0915”(physical association)	0.560
CLDN9	MAL	psi-mi:“MI:0915”(physical association)	0.560
CLDN9	LPAR3	psi-mi:“MI:0915”(physical association)	0.560
CLDN9	AOC3	psi-mi:“MI:0915”(physical association)	0.560
CLDN9	CYB561	psi-mi:“MI:0915”(physical association)	0.560
CLDN9	IGFBP5	psi-mi:“MI:0915”(physical association)	0.560
CLDN9	EMP1	psi-mi:“MI:0915”(physical association)	0.560
CLDN9	MALL	psi-mi:“MI:0915”(physical association)	0.560
CLDN9	ERMP1	psi-mi:“MI:0915”(physical association)	0.560
CLDN9	RPRM	psi-mi:“MI:0915”(physical association)	0.560
CLDN9	GRM2	psi-mi:“MI:0915”(physical association)	0.560
CLDN9	PLPP6	psi-mi:“MI:0915”(physical association)	0.560
CLDN9	ARLN	psi-mi:“MI:0915”(physical association)	0.560
CLDN9	VSTM1	psi-mi:“MI:0915”(physical association)	0.560
CLDN9	ADIPOQ	psi-mi:“MI:0915”(physical association)	0.560
CLDN9	BNIP3	psi-mi:“MI:0915”(physical association)	0.560
CLDN9	STX8	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (17): CLDN9 (Two-hybrid), CLDN9 (Two-hybrid), CLDN9 (Two-hybrid), CLDN9 (Two-hybrid), CLDN9 (Two-hybrid), CLDN9 (Two-hybrid), CLDN9 (Two-hybrid), CLDN9 (Two-hybrid), CLDN9 (Two-hybrid), CLDN9 (Two-hybrid), CLDN9 (Two-hybrid), CLDN9 (Two-hybrid), CLDN9 (Two-hybrid), CLDN9 (Two-hybrid), CLDN9 (Two-hybrid)

ESM2 similar proteins: A0A8C0N7E5, C3VMW3, D3ZQJ0, O00501, O14493, O15551, O19005, O35054, O35912, O54942, O88551, O95471, O95484, O95832, P56745, P56746, P56747, P56748, P56750, P78369, Q2HJ22, Q2KIY2, Q3B7N4, Q5E9L0, Q5QT56, Q5R8E5, Q63400, Q6BBL6, Q6DHB5, Q6DHP1, Q6L708, Q765N9, Q8BXA6, Q8N6F1, Q95KM5, Q9D1D1, Q9ET38, Q9JKD6, Q9QYW5, Q9YH90

Diamond homologs: A0A8C0N7E5, A6NM45, C3VMW3, C9JDP6, D3ZQJ0, O00501, O14493, O15551, O19005, O35054, O54942, O75508, O88551, O88552, O95471, O95484, O95500, O95832, P56745, P56746, P56747, P56748, P56750, P56856, P56857, P56880, P57739, P78369, Q0VCN0, Q2HJ22, Q2KIY2, Q3B7N4, Q3MHK4, Q4R3L1, Q5E9L0, Q5I0E5, Q5QT56, Q5R8E5, Q60771, Q63400

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 97 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	5	46.0×	3e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	43.9×	3e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	43.9×	3e-06
Assembly and cell surface presentation of NMDA receptors	10	40.9×	3e-12
Dopamine Neurotransmitter Release Cycle	5	40.0×	4e-06
Long-term potentiation	5	38.4×	4e-06
Neurexins and neuroligins	11	34.9×	2e-12
Protein-protein interactions at synapses	7	30.0×	2e-07

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	11	68.7×	2e-15
protein localization to synapse	6	49.4×	4e-07
receptor clustering	7	47.0×	4e-08
regulation of postsynaptic membrane neurotransmitter receptor levels	6	32.0×	4e-06
cell-cell adhesion	9	9.8×	3e-05
protein-containing complex assembly	8	9.8×	1e-04
chemical synaptic transmission	9	7.5×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

73 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	57
Likely benign	10
Benign	1

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
984737	NM_020982.4(CLDN9):c.86del (p.Leu29fs)	Pathogenic
3250379	NM_020982.4(CLDN9):c.346C>T (p.Arg116Cys)	Likely pathogenic

SpliceAI

89 predictions. Top by Δscore:

Variant	Effect	Δscore
16:3013497:G:GA	donor_gain	0.9300
16:3013496:T:TA	donor_gain	0.9200
16:3013816:GTGGC:G	donor_gain	0.8600
16:3013817:TGGCT:T	donor_gain	0.8600
16:3013818:GGCTG:G	donor_gain	0.8600
16:3013836:G:GT	donor_gain	0.7800
16:3013498:GT:G	donor_gain	0.7600
16:3013157:CG:C	acceptor_gain	0.7400
16:3013798:G:GT	donor_gain	0.6900
16:3013485:G:GA	donor_gain	0.6800
16:3013820:C:G	donor_gain	0.6300
16:3013819:GC:G	donor_gain	0.6000
16:3013581:G:GT	acceptor_gain	0.5800
16:3013495:G:GT	donor_gain	0.5000
16:3013638:G:GA	acceptor_gain	0.4900
16:3013155:CGCG:C	acceptor_gain	0.4700
16:3013158:G:GC	acceptor_gain	0.4600
16:3014004:GGAC:G	donor_gain	0.4600
16:3014293:GCC:G	acceptor_gain	0.4600
16:3014294:CCC:C	acceptor_gain	0.4600
16:3013157:C:CA	acceptor_gain	0.4500
16:3013488:GGCCC:G	donor_gain	0.4400
16:3013221:GAAC:G	donor_gain	0.4300
16:3013459:ACC:A	donor_gain	0.4300
16:3013452:G:GT	donor_gain	0.4100
16:3013563:C:CT	acceptor_gain	0.4100
16:3013582:C:CC	acceptor_gain	0.4000
16:3013583:C:CC	acceptor_gain	0.4000
16:3013154:CCGCG:C	acceptor_gain	0.3900
16:3013585:CAGGA:C	acceptor_gain	0.3700

AlphaMissense

1348 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:3013465:T:C	F35L	0.998
16:3013467:C:A	F35L	0.998
16:3013467:C:G	F35L	0.998
16:3013507:G:C	G49R	0.998
16:3013801:T:C	F147L	0.998
16:3013803:C:A	F147L	0.998
16:3013803:C:G	F147L	0.998
16:3013833:G:C	K157N	0.997
16:3013833:G:T	K157N	0.997
16:3013507:G:T	G49C	0.996
16:3013513:T:A	W51R	0.996
16:3013513:T:C	W51R	0.996
16:3013450:T:A	W30R	0.995
16:3013450:T:C	W30R	0.995
16:3013452:G:C	W30C	0.995
16:3013452:G:T	W30C	0.995
16:3013515:G:C	W51C	0.995
16:3013515:G:T	W51C	0.995
16:3013552:T:A	C64S	0.995
16:3013553:G:C	C64S	0.995
16:3013843:G:A	G161R	0.995
16:3013843:G:C	G161R	0.995
16:3013523:G:A	C54Y	0.994
16:3013843:G:T	G161W	0.994
16:3013411:G:C	G17R	0.993
16:3013844:G:A	G161E	0.993
16:3013522:T:C	C54R	0.992
16:3013552:T:C	C64R	0.992
16:3013802:T:G	F147C	0.992
16:3013864:T:A	W168R	0.992

dbSNP variants (sampled 300 via entrez): RS1000419818 (16:3011243 C>T), RS1002111012 (16:3014343 A>C), RS1002201661 (16:3012913 G>A,C,T), RS1002891854 (16:3012741 T>C), RS1004046826 (16:3012169 C>T), RS1005186503 (16:3011770 G>A), RS1005733214 (16:3012938 C>T), RS1005785558 (16:3013112 C>A,G), RS1006123921 (16:3013926 C>A,T), RS1006668263 (16:3011269 C>T), RS1007062296 (16:3013465 T>A), RS1008648622 (16:3013953 G>A,C), RS1009565023 (16:3012594 G>A,T), RS1009684231 (16:3013638 G>A,C), RS1009913106 (16:3013319 C>T)

Disease associations

OMIM: gene MIM:615799 | disease phenotypes: MIM:274600, MIM:619093

GenCC curated gene-disease

Disease	Classification	Inheritance
hearing loss, autosomal recessive 116	Moderate	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
hearing loss, autosomal recessive 116	Moderate	AR

Mondo (4): Pendred syndrome (MONDO:0010134), hearing loss, autosomal recessive 116 (MONDO:0033670), hearing loss disorder (MONDO:0005365), nonsyndromic genetic hearing loss (MONDO:0019497)

Orphanet (2): Pendred syndrome (Orphanet:705), Rare non-syndromic genetic deafness (Orphanet:87884)

HPO phenotypes

5 total (5 of 5 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000407	Sensorineural hearing impairment
HP:0001263	Global developmental delay
HP:0002403	Positive Romberg sign
HP:0003621	Juvenile onset

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
C580334	Nonsyndromic Deafness (supp.)
C536648	Pendred syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	decreases expression, increases expression	3
Acetaminophen	increases expression, decreases expression	2
aristolochic acid I	increases expression	1
sotorasib	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
ethyl-p-hydroxybenzoate	increases expression	1
trichostatin A	decreases methylation, increases expression, affects cotreatment	1
sodium arsenite	decreases expression	1
licochalcone B	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Azacitidine	decreases methylation, increases expression, affects cotreatment	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	affects cotreatment, decreases expression	1
Dimethyl Sulfoxide	decreases reaction, decreases methylation, increases expression, decreases expression	1
Estradiol	decreases expression	1
Hydrogen Peroxide	decreases expression, decreases reaction, affects expression	1
Methotrexate	decreases expression	1
Ozone	affects expression, increases abundance	1
Smoke	decreases expression	1
Triclosan	decreases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases methylation	1
Copper Sulfate	increases expression	1

Cellosaurus cell lines

5 cell lines: 2 cancer cell line, 2 transformed cell line, 1 spontaneously immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_C3VE	HT-1080/hCLDN-9	Cancer cell line	Male
CVCL_D3PR	CHO/CLDN9	Transformed cell line	Female
CVCL_E1TT	HAP1 CLDN9 (-)	Cancer cell line	Male
CVCL_E6Q0	Genomeditech CHO-K1 H_CLDN9	Spontaneously immortalized cell line	Female
CVCL_E6TR	Genomeditech HEK-293 H_CLDN9-eGFP	Transformed cell line	Female

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00205881	PHASE4	COMPLETED	Bilateral Benefit in Adult Users of the HiRes 90K Bionic Ear System
NCT00331539	PHASE4	UNKNOWN	Relationship Between Auto NRT and Behavioural T & C Levels With the Nucleus Freedom Cochlear Implant
NCT00424307	PHASE4	UNKNOWN	Bilateral Cochlear Implant Benefit in Young Children
NCT00765635	PHASE4	COMPLETED	Chlorobutanol, Potassium Carbonate, and Irrigation in Cerumen Removal
NCT03321006	PHASE4	COMPLETED	Treating Hearing Loss to Improve Mood and Cognition in Older Adults
NCT01499901	PHASE3	WITHDRAWN	Comparison of the Bilateral Sequential and Simultaneous Cochlear Implantation in the Deaf Children
NCT02561091	PHASE3	COMPLETED	AM-111 in the Treatment of Acute Inner Ear Hearing Loss
NCT03331627	PHASE3	COMPLETED	Safety and Efficacy of STR001-IT and STR001-ER in Patients With SSHL
NCT05532657	PHASE3	ACTIVE_NOT_RECRUITING	ACHIEVE Brain Health Follow-Up Study
NCT00013455	PHASE2	COMPLETED	Quantifying Auditory Perceptual Learning Following Hearing Aid Fitting
NCT00323427	PHASE2	COMPLETED	Clinical Trial of the Living Well With Hearing Loss Workshop
NCT00552786	PHASE2	COMPLETED	Antioxidation Medication for Noise-induced Hearing Loss
NCT00802425	PHASE2	COMPLETED	Efficacy of AM-111 in Patients With Acute Sensorineural Hearing Loss
NCT01139281	PHASE2	COMPLETED	The Protective Effect of Ginkgo Biloba Extract on Cisplatin-induced Ototoxicity in Humans
NCT01451853	PHASE2	UNKNOWN	SPI-1005 for Prevention and Treatment of Chemotherapy Induced Hearing Loss
NCT01588925	PHASE2	COMPLETED	Hearing Preservation Using Dexamethasone and Hyaluronic Acid for Cochlear Implantation
NCT01773278	PHASE2	RECRUITING	Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
NCT02832128	PHASE2	COMPLETED	Evaluating Possible Improvement in Speech and Hearing Tests After 28 Days of Dosing of the Study Drug AUT00063 Compared to Placebo (QuicKfire)
NCT04915183	PHASE2	RECRUITING	Atorvastatin to Reduce Cisplatin-Induced Hearing Loss Among Individuals With Head and Neck Cancer
NCT05258773	PHASE2	COMPLETED	Evaluation of the Presence of SENS-401 in the Perilymph
NCT06340633	PHASE2	RECRUITING	SPI-1005 in Adults Receiving Cochlear Implant
NCT00582946	PHASE1	COMPLETED	Wide-Bandwidth Open Canal Hearing Aid For Better Multitalker Speech Understanding
NCT00584155	PHASE1	WITHDRAWN	Protection From Cisplatin Ototoxicity by Lactated Ringers
NCT01206829	PHASE1	UNKNOWN	Hearing Impairment, Cognitive Therapy and Coping
NCT01256229	PHASE1	COMPLETED	Outcomes In Children With Developmental Delay And Deafness
NCT01343394	PHASE1	WITHDRAWN	Safety of Autologous Human Umbilical Cord Blood Mononuclear Fraction to Treat Acquired Hearing Loss in Children
NCT01452607	PHASE1	COMPLETED	Study to Evaluate the Safety and Pharmacokinetics of SPI-1005
NCT02259595	PHASE1	COMPLETED	Study to Determine the Safety, Tolerability, and Pharmacokinetic Profile of HPN-07 and HPN-07 Plus NAC
NCT04041440	PHASE1	COMPLETED	Speech Recognition Training in Children With Hearing Loss
NCT07218913	PHASE1	RECRUITING	Testing the Addition of Pedmark to Cisplatin Chemotherapy for Reducing Drug-Induced Ear Damage in Men With Stage II-III Metastatic Testicular Germ Cell Tumors
NCT05970445	Not specified	UNKNOWN	Clinical Phenotypic Characteristics of SC26A4
NCT00486577	PHASE2/PHASE3	COMPLETED	Chronic Electrical Stimulation of the Auditory Cortex for Intractable Tinnitus
NCT00789061	PHASE2/PHASE3	UNKNOWN	Applying Proton Pump Inhibitor to Prevent and Treat Acute Fluctuating Hearing Loss in Patients With SLC26A4 Mutation
NCT01423409	PHASE2/PHASE3	COMPLETED	Multicenter Trial Assessing an Innovative VAS of Pain Among Deaf People
NCT05786378	PHASE2/PHASE3	UNKNOWN	Assessment of The Efficacy of Intratympanic Platelet Rich Plasma for Treatment of Sensorineural Hearing Loss.
NCT01108601	PHASE1/PHASE2	UNKNOWN	Transtympanic Ringer’s Lactate for the Prevention of Cisplatin Ototoxicity
NCT01621256	PHASE1/PHASE2	COMPLETED	Efficacy, Safety, and Tolerability of Ancrod in Patients With Sudden Hearing Loss
NCT06370351	PHASE1/PHASE2	RECRUITING	A Phase I/II Clinical Trial with SENS-501 in Children Suffering from Severe to Profound Hearing Loss Due to Otoferlin (OTOF) Mutations
NCT06545175	PHASE1/PHASE2	RECRUITING	Intracochlear Application of VSF1.01 for the Reduction of Cochlear Implant Surgery Related Trauma
NCT07304024	PHASE1/PHASE2	RECRUITING	A Treatment for a Form of Age-Related Central Auditory Processing Disorder Consisting of Clemastine Fumarate Plus Engineered Sound